Lifetime exposure to smoking, epigenetic aging, and morbidity and mortality in older adults.

BACKGROUND: Cigarette smoke is a major public health concern. Epigenetic aging may be an important pathway by which exposure to cigarette smoke affects health. However, little is known about how exposure to smoke at different life stages affects epigenetic aging, especially in older adults. This study examines how three epigenetic aging measures (GrimAge, PhenoAge, and DunedinPoAm38) are associated with parental smoking, smoking in youth, and smoking in adulthood, and whether these epigenetic aging measures mediate the link between smoke exposure and morbidity and mortality. This study utilizes data from the Health and Retirement Study (HRS) Venous Blood Study (VBS), a nationally representative sample of US adults over 50 years old collected in 2016. 2978 participants with data on exposure to smoking, morbidity, and mortality were included.

RESULTS: GrimAge is significantly increased by having two smoking parents, smoking in youth, and cigarette pack years in adulthood. PhenoAge and DunedinPoAm38 are associated with pack years. All three mediate some of the effect of pack years on cancer, high blood pressure, heart disease, and mortality and GrimAge and DunedinPoAm38 mediate this association on lung disease.

CONCLUSIONS: Results suggest epigenetic aging is one biological mechanism linking lifetime exposure to smoking with development of disease and earlier death in later life. Interventions aimed at reducing smoking in adulthood may be effective at weakening this association.